Cyclic AMP–dependent protein kinase A–cyclic AMP response element-binding protein pathway (cAMP–PKA–CREB pathway)

The cyclic AMP–dependent protein kinase A–cyclic AMP response element-binding protein pathway (cAMP–PKA–CREB pathway) is a ubiquitous intracellular signaling cascade that translates external signals, typically via G protein-coupled receptors, into changes in gene expression. Upon GPCR activation, adenylyl cyclase converts ATP to cyclic AMP (cAMP), which activates protein kinase A (PKA). Activated PKA translocates to the nucleus and phosphorylates the transcription factor CREB, which then binds to specific DNA motifs (cAMP response elements; CRE) and regulates the transcription of a wide variety of genes involved in cell metabolism, proliferation, survival, differentiation, neural plasticity, and immune responses. Dysregulation of the pathway is implicated in cancer, diabetes, inflammation, and neurologic diseases[1][2][3][4][5][7][8].

Other names

cAMP–PKA–CREB signaling pathwaycyclic AMP/PKA/CREB pathwayadenosine 3′,5′-cyclic monophosphate–protein kinase A–CREB pathway

Inhibition of cAMP degradation (by phosphodiesterase inhibitors) increases pathway signaling; Inhibition of PKA kinase activity (by H89, KT-5720) blocks cAMP downstream effects; cAMP analogs directly activate PKA; Upstream GPCR modulation influences cAMP synthesis.